Understanding vaccine development Firdausi Qadri Director, Centre for Vaccine Sciences International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)
Outline of this talk 1. Understanding disease burden and the need for vaccines 2. Different stages of development of vaccines 3. Funding, risks and challenges
Understanding need for vaccines Knowledge of natural history of infection and the spectrum of illness Information on incidence or prevalence of the infectious disease in consideration Disease burden data- Although disease may be prevalent, accurate data on burden of disease may be missing due to lack of surveillance at country level
Vaccine Development Laboratory and animal studies Exploratory stage- basic and applied research on vaccine components, protective antigen and host responses Pre-clinical stage- animal experimentation to determine mode of action, route of administration, protection, dosage Availability of existing animal model and a correlate of protection can accelerate vaccine development
Studies in human participants Phase I- Safety and immunogenicity trials on relatively limited number of participants (1-2 yr: n=20-80) Human Challenge studies (2-3yr: n=10-30) Moving to larger Phase II studies (2-3 yr: n=100-300) Phase III, protective efficacy trials (3-5 yr: n=1000-200,000) Licensure and WHO prequalification (1-2 yr) Phase IV effectiveness studies (2-4 yr) Commercialization and marketing (variable) Post marketing surveillance and more clinical studies This path can take 10 years for vaccines needed for mid level to high income countries: when targeted for low income countries the process may get delayed to over 20-30 years or even over 100 years
Cost of development of vaccines Research and discovery to product registration may cost $200m-500m Commercial realities have reduced private investment developing country spending is low but increasingly supported by funding from industrialized countries including public and private foundations Research and development requires industrial partner and manufacturer to decrease capital investment costs and for need to produce vaccines in accordance with good manufacturing practices
What are the risks involved in vaccine development? it is a lengthy and complex procedure with many risks many preclinical and Phase I-III studies on vaccines do not result in a registered vaccine the probability of preclinical vaccine reaching market have a 5:1 odds of success ; that is for every vaccine marketed there should be 4-5 vaccines under development added to this is the political/economic issues and uncertainties in end-consumer use Serdobova and Kieny, 2006
Other challenges faced in development of vaccines Vaccines may not be equally efficacious in all settings Not enough known about vaccine composition, dosage and immunization schemes for developing country populations immunogenicity and protection can be lower in malnourished populations Negative effect of concomitant infection on vaccine take rates- TB, HIV, malaria, enteric infections Primed versus naïve or children versus adult responses can be different In country and local production of vaccines may be hindered by lack of regulatory authorities leading to delay in WHO prequalification and availability
Conclusions and the way forward Vaccine development and production need to be enhanced Basic research and understanding of region and country specific needs for composition of vaccines and related host responses Developing country producers need to be encouraged to enhance capacity with funding and technology transfer support This can boost vaccine usage regional and country specific vaccine candidates efficacious shipment costs requirement of cold room storage capacity Can result in savings to both GAVI and country funds and accelerate access to appropriate products for diverse populations to meet MDG goals